Capsaicin-induced stimulation of the guinea-pig atrium

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Abstract
1. The mechanism underlying the positive inotropic and chronotropic effects of capsaicin were investigated using the spontaneously beating guinea-pig atrium in vitro. 2. Capsaicin induced a long-Lasting stimulatory effect (threshold dose 10−9 M). Tetrodotoxin, phentolamine, 6-OHDA, mepyramine plus cimetidine, methysergide-, indomethacin-, somatostatin-or morphine pretreatment and local treatment with capsaicin on the vagal nerves did not reduce the capsaicin response, while it was abolished up to 1 month after systemic capsaicin pretreatment. 3. The capsaicin response was subject to a rapid tachyphylaxis. During capsaicin tachyphylaxis, the positive inotropic and chronotropic effects of noradrenaline, serotonin and histamine were unchanged. 4. Various neuropeptides were investigated with regard to cardiac activity. Physalaemin, eledoisin and somatostatin had negative inotropic and chronotropic effects. Substance P, bombesin, kassinin, CCK-8 or PHI (up to 10−6 M of each) did not cause any detectable response on the guinea-pig auricle, while the substance P antagonist [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP induced a long-lasting stimulation of heart activity, VIP also stimulated the heart. 5. Various adenyl compounds were also tested. Adenosine, AMP, ADP, ATP and β-, γ-methylene ATP had negative chronotropic and inotropic effects, while α-, β-methylene ATP induced a stimulatory response. During α-, β-methylene ATP tachyphylaxis, the auricles still responded to capsaicin. The inhibitory effects of adenosine and ATP analogues were antagonized by theophylline and 8-p-sulfophenyl theophylline. Capsaicin induced a small release of labelled nucleotides from 3(H)-adenine-prelabelled atria from control, but not from capsaicin-pretreated animals. 6. GTP, aspartate and kainic acid (up to 10−4 M) had no effect on the guinea-pig atrium, while glutamate had a negative inotropic action. 7. In conclusion, the present findings show a specific stimulatory action of capsaicin on heart function. This effect does not seem to be mediated via any classical transmitter, including substance P and ATP. The capsaicin response was abolished by capsaicin pretreatment, which is known to cause degeneration of chemosensitive nerves in the heart. This suggests that capsaicin may release other bioactive substances than substances P from sensory nerves. A direct action of capsaicin on cardiac myocytes cannot be excluded. A desensitization phenomenon would then also occur on possible receptive sites for capsaicin on the myocytes. Capsaicin pretreatment may thus induce very long-lasting, specific, functional changes in heart function.